WE ISOLATED and characterised a novel gene called Sox18. In situ hybridization experiments in mouse embryos have revealed a striking correlation between sites of Sox18 expression and the formation of endothelial cells of the developing vasculature throughout the embryo (see Figure). We have found that Sox18 expression is lacking in embryos deficient in Flk1, confirming a role for Sox18 in the VEGF-Flk1 pathway of endothelial cell differentiation and mitogenesis. In addition we have shown that Sox18 mutations underlie the mouse mutant Ragged (Ra), which is characterized by edema suggesting blood vessel and/or lymphatic dysfunction.

The aim of this project is to clarify the role of Sox18 in the development and function of the vascular and lymphatic system. We are thoroughly investigating the expression of Sox18 during blood vessel development in embryos, adults and tumours, and have inactivated Sox18 by homologous recombination.

The overall hypothesis being tested is that Sox18 is an important component of the molecular pathway of blood vessel development, and as such may be an entry point to novel therapeutic strategies for vascular diseases, or other diseases in which blood vessels play an important part, such as cancer. This work may in the longer term suggest new avenues of therapeutic intervention that may be applicable to suppression of tumour growth and metastasis.

Key technologies

• In situ hybridization, histological analysis, immunohistochemistry, cell culture angiogenesis assays, gene knockouts, protein biochemistry.

Key publications